Allotype-specific immunoregulation of autoantibody production by host B cells in chronic graft-versus host disease.
A chronic graft-vs-host (GVH) reaction induced in nonautoimmune mice by the transfer of Ia-incompatible spleen cells results in a syndrome that closely resembles SLE in the spectrum of autoantibodies and immunopathology. We have utilized Ia- and Igh-congenic strains to study the immunoregulation of autoantibody-producing B cells in this model. We have found that the autoantibodies are produced almost entirely by the host B cells. The transferred donor B cells contributed neither to the autoimmune response nor to the total serum Ig, with rare exceptions. The donor cell population did, however, exert an Igh allotype-specific immunoregulatory effect on the host B cells. For example, in allotype-heterozygous recipients, the autoantibodies were preferentially made by those host cells that expressed the donor allotype, whereas those host B cells that expressed nondonor allotype were relatively suppressed. In allotype-homozygous recipients, the donor cells frequently suppressed the host IgG2a allotype completely. This suppression sometimes prevented the IgG antichromatin response, although in other cases the response occurred with the use of a different isotype. In a final set of experiments, a chronic GVH reaction was induced in which both the donors and the recipients were Igh allotype heterozygous and yet differed at Ia. In this case, no donor influence on allotype should be expected; yet the IgG2a autoantibodies were clearly skewed toward the b allotype. These results show that host B cells play a unique role in the GVH autoimmune syndrome. In addition, they are immunoregulated in allotype-specific manners, some of which presumably involve interaction with donor T cells.
Morris
S C
SC
Department of Microbiology/Immunology, University of North Carolina, Chapel Hill 27599.
Cheek
R L
RL
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D002843:Chromatin / Q000276:immunology; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000276:immunology*; D006579:Heterozygote; D007126:Immunoglobulin Allotypes / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains
D001323:Autoantibodies; D002843:Chromatin; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G